wk-x-34 and Neoplasms

wk-x-34 has been researched along with Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for wk-x-34 and Neoplasms

Article	Year
Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors. Bioorganic & medicinal chemistry, 2016, 05-15, Volume: 24, Issue:10 A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzamides; Click Chemistry; Doxorubicin; Drug Design; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; K562 Cells; Neoplasms; Structure-Activity Relationship; Tetrahydroisoquinolines	2016
Discovery of novel P-glycoprotein-mediated multidrug resistance inhibitors bearing triazole core via click chemistry. Chemical biology & drug design, 2014, Volume: 84, Issue:2 A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors bearing a triazol-phenethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo-sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P-gp-mediated MDR inhibitor. Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzamides; Click Chemistry; Doxorubicin; Drug Resistance, Multiple; Humans; K562 Cells; Neoplasms; Triazoles	2014

Article

Year

Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

Bioorganic & medicinal chemistry, 2016, 05-15, Volume: 24, Issue:10

A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors.

Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzamides; Click Chemistry; Doxorubicin; Drug Design; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; K562 Cells; Neoplasms; Structure-Activity Relationship; Tetrahydroisoquinolines

2016

Discovery of novel P-glycoprotein-mediated multidrug resistance inhibitors bearing triazole core via click chemistry.

Chemical biology & drug design, 2014, Volume: 84, Issue:2

A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors bearing a triazol-phenethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo-sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P-gp-mediated MDR inhibitor.

Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzamides; Click Chemistry; Doxorubicin; Drug Resistance, Multiple; Humans; K562 Cells; Neoplasms; Triazoles

2014